tbuckley/cabot-search huggingface dataset:
PB1956: EVALUATION OF AN INNOVATIVE NEW METHOD FOR QUANTITATION OF PLASMA CELLS ON CD138 IMMUNOHISTOCHEMISTRY
Authors: E. Gantana, N. Mashigo, I. Abdullah, E. Musekwa, R. Lohlun, E.-M. Nell, C. Chetty, M. Ntobongwana, Z. Chapanduka
Journal: HemaSphere (2022)

Background: The estimation of plasma cells in bone marrow biopsies using CD138 immunohistochemistry, as proposed by the World Health Organization (WHO), has become popular over the last few years. The determination of the plasma cell percentage plays a vital role in categorising patients into different diagnostic and prognostic groups at diagnosis and evaluating response to treatment during follow-up, which guides management protocols. There is currently no reference method (gold standard) for the estimation of plasma cells. The most commonly used method involves scanning of slides and expression of plasma cell numbers as a percentage of all nucleated cells (overview estimate). Aims: To compare the frequently used CD138 immunohistochemistry- based method of plasma cell quantitation, to a proposed new method, using interobserver and intraobserver concordance parameters. Methods: Archival CD138 immunohistochemically stained slides made from paraffin- embedded bone marrow biopsies of 33 patients with a confirmed diagnosis of multiple myeloma were used. Light microscopic examination was performed using low magnification lenses (10×) for both the overview estimation method (method A) and the new method (method B), and high magnification lenses (50×), for method B only. For method B, reviewers selected three areas with low, intermediate and high plasma cell densities using 10× lenses. Using a well- defined technique, the 50× lens was then used to count plasma cells as a percentage of all nucleated cells. After blinded relabelling of all the slides, the nine reviewers repeated the plasma cell quantitation using both methods. The plasma cell counts were obtained, and the review times were recorded. Results: Overall intraobserver concordance was comparable for method A (concordance correlation coefficient (CCC)=0.840) and method B (CCC=0.733). Interobserver concordance for method A (intraclass correlation coefficient (ICC)=0.793 and 0.713) and method B (ICC=0.657 and 0.658) indicated high similarity between reviewers. Method A showed poor interobserver concordance (ICC=0.105) at low plasma cell densities. Summary/Conclusion: The new method is comparable to the frequently used overview estimation method in terms of intraobserver and interobserver concordance, and cost. The new method has superior interobserver concordance at low plasma cell densities. The new method appears more amenable to digital scanning and analysis.
P1688: VKORC1 -1639 G/A GENE POLYMORPHISM CAN MODULATE THE RISK OF VENOUS THROMBOEMBOLISM IN ELDERLY PATIENTS WITH FV LEIDEN MUTATION
Authors: S. Kapustin, A. Chechulova, J. Drijun, S. Svitina, V. Burakov, V. Soroka, V. Soldatenkov, L. Papayan
Journal: HemaSphere (2022)

Background: Vitamin K plays important role in hemostasis by activating both procoagulant (FII, VII, IX, X) and anticoagulant (proteins C, S, Z) factors. Vitamin K-epoxide reductase 1 (VKORC1) G-1639A gene polymorphism affects enzyme activity and bioavailability of vitamin K. Little is known about the role of the VKORC1 G-1639A variation in venous thromboembolism (VTE) development, in particular, in patients with inherited thrombophilia. Aims: To study the role of the VKORC1 -1639G/A gene polymorphism in VTE development in patients from North-Western Russia. Methods: We included 600 VTE patients (294 men and 306 women, mean age 43.6±15.3 years) originated from the North-Western region of Russia in the study. The control group (CG) consisted of 200 healthy individuals of the same origin. Genotyping for the VKORC1 -1639 G/A, FII 20210 G/A and FV 1691 G/A variations was performed by PCR-RFLP. Intergroup differences in genotype frequencies were assessed by Fisher’s exact test. The study was approved by the local ethical committee. Results: Distribution of the VKORC1 G-1639A gene variants was similar in both VTE patients and controls. In the group of patients without FII and FV gene mutations, the frequency of the VKORC1 -1639AA genotype was almost equal to that in CG (17.1% vs. 16.5%, respectively). VKORC1 -1639AA genotype frequency in patients with the FV Leiden was 4-fold higher than in those having the FII G20210A mutation (19.6% vs. 4.4%, respectively; OR=5.2; p=0.021). Notably, among patients having FV Leiden variant, the VKORC1 -1639AA genotype frequency was much higher in the group with late-onset disease (after 45 years) compared to young VTE patients (31.6% vs. 11.9%; OR=3.4; p=0.02). Thus, in elderly VTE patients with FV Leiden, the VKORC1 -1639AA variant was almost 2-fold overrepresented when compared to CG (31.6% vs. 16.5%; OR=2.4; p=0.033). Summary/Conclusion: We suggest that the VKORC1 -1639AA genotype could increase VTE risk in elderly patients with the FV Leiden mutation.
P1607: EPICOVIDEHA KIDS: A READY TO USE PLATFORM FOR EPIDEMIOLOGICAL STUDIES IN PEDIATRIC HEMATOLOGICAL PATIENTS WITH COVID-19
Authors: J. Salmanton-García, A. Busca, O. A. Cornely, M. Hoenigl, N. Klimko, P. Koehler, F. Marchesi, A. Pagliuca, F. Passamonti, T. E. Zaoutis, L. Pagano, Z. D. Pana
Journal: HemaSphere (2022)

Background: The coronavirus disease 2019 (COVID-19) pandemic has direct impact on patients with active hematological malignancies (HM), who are at a continuous risk for severe disease course and delay of chemotherapy. The COVID-19 study of the European Hematology Association (EPICOVIDEHA) was initiated in February 2020 by an international steering committee. As of November 2021, more than 4,500 adult cases from 35 countries in five continents have been registered. From January 2022, EPICOVIDEHA will broaden its target population, in order to include children too, establishing the EPICOVIDEHA Kids registry. Aims: The aim is to enhance the knowledge of the outcome and clinical management of these patients. The incidence of severe COVID-19, admission to intensive care units (ICU), estimation of pre-existing comorbidities, or associated mortality rate will also be evaluated. Methods: The EPICOVIDEHA Kids survey will be online accessible at www.clinicalsurveys.net. All data will be collected anonymously: demographics, underlying diseases, hematological malignancy, COVID-19 infection, and outcome. Inclusion criteria will be: age below 18 years, active HM within the last 5 years prior to COVID-19, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test. Each documented patient will be reviewed for data completeness and coherence by a panel of experts. Results: A general publication with the data from all patients will be performed at the end of 2022. Additionally, subset analyses on specific cutting-edge topics might be run after the proposal of any participant with the previous approval of the steering committee of the survey. Summary/Conclusion: EPICOVIDEHA Kids is a ready-to-use survey, whose focal point is to gather epidemiological data from pediatric hematological populations and COVID-19. This study will help to better understand the features of these patients and to ameliorate their clinical management. Additionally, EPICOVIDEHA Kids will enable the partnership of international groups of hematologists and infectious diseases specialists, in order to improve the clinical management of HM patients with COVID-19.
MXene‐Enhanced Chitin Composite Sponges with Antibacterial and Hemostatic Activity for Wound Healing (Adv. Healthcare Mater. 12/2022)
Authors: Shanshan Li, Bin Gu, Xiaoyun Li, Shuwei Tang, Lu Zheng, Eduardo Ruiz‐Hitzky, Zeyu Sun, Changliang Xu, Xiaoying Wang
Journal: Advanced Healthcare Materials (2022)
Interim Analysis of Acute Hepatitis of Unknown Etiology in Children Aged &lt;10 Years — United States, October 2021–June 2022
Authors: Jordan Cates, Julia M. Baker, Olivia Almendares, Anita K. Kambhampati, Rachel M. Burke, Neha Balachandran, Eleanor Burnett, Caelin C. Potts, Sarah Reagan-Steiner, Hannah L. Kirking, David Sugerman, Umesh D. Parashar, Jacqueline E. Tate, Melissa M. Coughlin, Bettina Bankamp, Julu Bhatnagar, Lindsey Blythe Coulter Estetter, Luciana Silva-Flannery, Hannah Bullock, Negar Rassaei, Everardo M. Vega, Xiaoyan Lu, Erin R. McKeever, Debra Wadford, Christina Morales, Chao-Yang Pan, Kirsten St. George, Daryl M. Lamson, L. Amanda Ingram, Theresa Dulski, Tameika Reed, Liam Hicks, J Bradford Bertumen, Bonnie L. Dao, Diana M. Tapay, Michael J. Kacka, Paul Gacek, Nikki M. Kupferman, Angeni Cordova, Ashley Gent, Kati Touchstone, Melissa Tobin-D’Angelo, Ami Gandhi, Kris Carter, Kathryn Turner, Lori Saathoff-Huber, Judy Kauerauf, Nicole Stone, Bethany Hodge, Julie Hand, Christine Nguyen, Juliana Jacoboski, Emer S. Smith, Chloe Manchester, Macey Ladisky, Genny Grilli, Alexandra Berkley, Jennifer Hanson, Carla Boutwell, Erin Ricketts, Lana Deyneka, Lindsey VanderBusch, Derek Julian, Matthew Donahue, Reed Magleby, Deepam Thomas, Anna M Stadelman, Ali Garcia, Bridget J. Anderson, Youjung Byun, Aprielle Wills, Page Keating, Brandi Taylor, Courtney Dewart, Mike Mannell, Lauren Orkis, Meghan Murray, Iris Cardona Gerena, Melissa Marzán Rodríguez, Patricia McAuley, Hayden Hedman, Jessica Schultz, Christa Cook, Ryan Wallace, Amelia Salmanson, Dawn Saady, Amanda Dodd, Kimberly Carlson, Thomas Haupt
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

On April 21, 2022, CDC issued a health advisory† encouraging U.S. clinicians to report all patients aged <10 years with hepatitis of unknown etiology to public health authorities, after identification of similar cases in both the United States (1) and Europe.§ A high proportion of initially reported patients had adenovirus detected in whole blood specimens, thus the health advisory encouraged clinicians to consider requesting adenovirus testing, preferentially on whole blood specimens. For patients meeting the criteria in the health advisory (patients under investigation [PUIs]), jurisdictional public health authorities abstracted medical charts and interviewed patient caregivers. As of June 15, 2022, a total of 296 PUIs with hepatitis onset on or after October 1, 2021, were reported from 42 U.S. jurisdictions. The median age of PUIs was 2 years, 2 months. Most PUIs were hospitalized (89.9%); 18 (6.1%) required a liver transplant, and 11 (3.7%) died. Adenovirus was detected in a respiratory, blood, or stool specimen of 100 (44.6%) of 224 patients.¶ Current or past infection with SARS-CoV-2 (the virus that causes COVID-19) was reported in 10 of 98 (10.2%) and 32 of 123 (26.0%) patients, respectively. No common exposures (e.g., travel, food, or toxicants) were identified. This nationwide investigation is ongoing. Further clinical data are needed to understand the cause of hepatitis in these patients and to assess the potential association with adenovirus.
P842: NOVEL MULTIFUNCTIONAL TETRAVALENT CD38 NKP46 FLEX-NK ENGAGERS ACTIVELY TARGET AND KILL MULTIPLE MYELOMA CELLS
Authors: L. Lin, H.-M. Chang, C. Nakid, S. Frankel, D. Wu, J. Kadouche, D. Teper, O. Mandelboim, J.-C. Bories, A. Arulanandam, W. Li
Journal: HemaSphere (2022)

Background: Given that CD38 is a clinically validated target for natural killer (NK) cell mediated cytotoxicity in multiple myeloma (MM), we sought to leverage our FLEX-NKTM platform to create a NK engager antibody targeting CD38. FLEX-NKTM is a proprietary platform for production of tetravalent IgG1-like multifunctional NK engager antibodies with a novel FLEX-linker to allow for simultaneous binding of both the targeted cancer cells and NK cells via the activation receptor NKp46. Aims: Derive preclinical proof of concept with CD38 targeted NK-cell engager bispecific antibody in Mulitple Myeloma Methods: CYT-338 was expressed in CHOZEN cells and purified by step column chromatography. PB-NK cells were purified from healthy donor blood. PB-NK cytotoxicity against MM tumors was evaluated in the presence of CYT-338 or isotype control antibodies at a fixed E/T ratio. CYT-338 pharmacokinetics in mice was evaluated following a single intravenous injection. Anti-tumor efficacy of CYT-338 was evaluated in NSG-mice injected with PB-NK cells and MM cell line MM1S expressing luciferase. CYT-338 mediated fratricide was evaluated in purified PB-NK's. CYT-338 cytokine release assessments and hemato-cytotoxicity was evaluated in-vitro in human PBMC assays. Results: CYT-338 showed dose dependent binding to CD38 expressing MM cell lines MM1S and KMS11 and no binding to a CD38 knock out MM.1S cell line. CYT-338 bound MM cell lines with ~ 2-fold higher mean fluorescence intensity than anti-CD38 monoclonal antibody (mAb) or daratumumab alone. Epitope mapping studies for our CD38 mAb binder using alanine scanning mutagenesis showed that amino acid S274 on CD38, critical for binding to daratumumab, is not important for CD38 binding, suggesting a distinct epitope detected by our CD38 binder. CYT-338 showed greater dose dependent NK cell redirected cytolysis, degranulation and cytokine production against MM1S cells compared to daratumumab. The CYT-338 pharmacokinetics study in mice showed a terminal half-life of 41 hrs. Preliminary in-vivo tumor model studies in NSG mice using PB-NK and CYT-338 injections showed tumor growth inhibition of MM1S tumor cells. Low NK cell fratricide was observed with CYT-338 while daratumumab showed significantly higher NK cell fratricide. In peripheral blood mononuclear cell hemato-toxicity studies, depletion of monocytes and NK cells were observed with daratumumab but no significant depletion was observed with CYT-338. Cytokine release assessment of CYT-338 in the human PBMC assay showed no evidence of cytokine release while high levels of cytokine release was observed with daratumumab, anti-CD28 (TGN1412) and CD3 antibody controls. Summary/Conclusion: These results suggest that the CYT-338 engager has a favorable NK cell engager profile for targeting CD38 expressing multiple myeloma distinct from daratumumab.
P1729: COMPARING THE PSYCHOSOCIAL IMPACTS OF THE COVID-19 PANDEMIC BETWEEN HAEMATOLOGICAL CANCER AND MYELOMA PATIENTS: FINDINGS FROM AN ONLINE SURVEY
Authors: S. J. Quinn, L. Anderson, L. Lohfeld, C. McShane
Journal: HemaSphere (2022)

Background: Haematological cancers are risk factors for severe COVID-19, and multiple myeloma (MM) patients may have further risk due to older age and susceptibility to infections. Aims: This study aims to understand the pandemic’s psychosocial impact and investigate whether MM patients experience extra stress compared to non-MM blood cancers. Methods: The IMPaCCT survey is an international, longitudinal online survey, open to cancer patients. The first survey captured the period April-July 2020 and used quantitative and qualitative measures of quality of life (QoL), including validated tools (WHOQOL-BREF and EQ-5D-5L). Results: Overall, 944 blood cancer patients responded (173 MM, 93 leukaemia, 117 lymphoma and 561 with a myeloproliferative neoplasm). Most were female, resided in the UK and did not live alone. Patients with MM were older (p<0.001) and less likely to be in employment (p<0.001), with more having received their cancer diagnoses in the last 5 years (p<0.001) than non-MM. Only three had a COVID diagnosis, with none having MM. Both groups reported high levels of concern about COVID, and this level was higher in MM; 50% of MM patients reported they were “extremely concerned”. In both groups, most said they would be less concerned about COVID if they didn’t have cancer. While 70% reported their QoL as good/very good across both groups, QoL was lower in physical, psychological and social domains than healthy pre-pandemic UK norms. Patients reported more satisfaction with environmental factors, such as living arrangement and access to services, however. There were high rates of anxiety/depression (67%, severe in 5%) and MM patients reported more issues with pain, mobility and engaging in their normal activities. Of the overall 84% who reported COVID had changed their lives, 63% found this hard to manage. Patients’ most trusted sources for information about COVID-19 were healthcare providers and scientists for both groups (90% and 86% reported high levels of trust, respectively). Interestingly, MM patients had more trust in their friends and family for COVID information (58% with high trust in MM, vs. 41% in non-MM; p<0.001). Regarding services, 43% had used telemedicine, with more MM patients using this service (61% of MM, 39% of non-MM). Most reported a positive experience. Health appointments were changed in format for most, and more often in MM patients (Changes: 69% of MM, 52% of non-MM) –with oncologist/haematologist visits most affected. In MM, treatments were changed, delayed or cancelled for 34%, which was significantly higher than non-MM (11%). Summary/Conclusion: This study summarises the self-reported impacts of COVID on psychosocial health and care access during the early pandemic in vulnerable patient groups; MM patients are also highlighted as especially vulnerable. Understanding the needs of these patients will enable healthcare providers to properly support them.
P1600: ANTIGENS OF THE DUFFY BLOOD GROUP SYSTEM AND RISK OF COVID-19 INFECTION
Authors: E. Poponina, E. Butina, A. Yovdiy, N. Minaeva
Journal: HemaSphere (2022)

Background: The Duffy blood group antigens are transmembrane glycoproteins, represented by two specificities (Fya and Fyb), also known as atypical chemokine receptor 1 (ACKR1). These structures are located not only on the red blood cell membrane, but also on the vascular endothelium, alveoli, epithelium of the renal tubules, and cerebellar neurons. The biological role of the Duffy system is to bind inflammatory chemokines and inhibit excessive leukocyte activation. The antigens also serve as receptors for viruses and malaria plasmodia to enter the cell. Therefore, the study of the participation of the Duffy blood group system in the development of COVID-19 infection is of particular interest. Aims: The aim of study was to compare the distribution of Duffy blood group antigens in individuals with and without COVID-19. Methods: The distribution of antigens of the Duffy blood group system was studied in 329 donors of blood components using equipment and reagents from BioRad (USA), OrthoClinicalDiagnostics (USA). The study was held from February 2020 to February 2021 (before the start of vaccination). 71 people had COVID-19, 258 didn’t. Age ranged from 20 to 63 years, median 38 years. Reliability of the diagnosis of COVID-19 is confirmed by a positive PCR test result and/or the presence of class G antibodies to the SARS-Cov2 virus. Statistical processing was performed using Fisher’s exact test. Results: The Fya antigen was detected in 75.2% of those who did not become ill and in 60.6% of those who had COVID-19 (p<0.05). The frequency of Fyb in donors with and without a new coronavirus infection was comparable, 78.9% and 77.5% respectively. The disease was less common in the individuals with the Fya phenotype. The COVID-19 incidence in them was 18.1%, while without the Fya antigen it reached 30.4% (p=0.02). Carriage of the Fyb antigen had no effect on the incidence of the disease, 21.9% in individuals with the presence of Fyb and 20.5% without it. Image:Summary/Conclusion: The Fya antigen showed a protective effect against COVID-19, its absence increased the risk of the disease by 1.5 times. The obtained results indicate the impact of blood group systems on the risk of COVID-19 infection, but the issue requires further study.
Abstract 628: Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies
Authors: Javier Glez-Vaz, Arantza Azpilikueta, Irene Olivera, Assunta Cirella, Álvaro Teijeira, Carmen Ochoa, Maite Álvarez, Iñaki Eguren, Carlos Luri-Rey, Miguel F. Sanmamed, Ignacio Melero
Journal: Cancer Research (2022)

Abstract Background: On the basis of efficacy in mouse tumor models, multiple CD137 (4-1BB) agonist agents are being preclinically and clinically developed. The costimulatory molecule CD137 is inducibly expressed as a transmembrane or as a soluble protein (sCD137). Moreover, the CD137 cytoplasmic signaling domain is a key part in approved Chimeric Antigen Receptors (CARs). Reliable pharmacodynamic biomarkers for CD137 ligation and co-stimulation of T cells will facilitate clinical development of CD137 agonists in the clinic. Methods: We used human and mouse CD8 T cells undergoing activation to measure CD137 transcription and protein expression levels determining both of the membrane-bound and soluble forms. In tumor-bearing mice plasma sCD137 concentrations were monitored upon treatment with agonist anti-CD137 mAbs. Human CD137 knock-in mice were treated with clinical-grade agonist anti-human CD137 (Urelumab). Sequential plasma samples were collected from the first patients intratumorally treated with Urelumab in the INTRUST clinical trial. Anti-Mesothelin CD137-encompassing CAR-transduced T cells were stimulated with mesothelin coated microbeads. sCD137 was measured by sandwich ELISAs and Luminex and flow cytometry was used to monitor CD137 surface expression. Results: CD137 co-stimulation upregulates transcription and protein expression of CD137 itself including sCD137 in human and mouse CD8 T cells. Immunotherapy with anti-CD137 agonist mAb resulted in increased plasma sCD137 in mice bearing syngeneic tumors. sCD137 induction is also observed in human CD137 knock-in mice treated with Urelumab and in mice transiently humanized with T cells undergoing CD137 co-stimulation inside subcutaneous implanted Matrigel® plugs. CD137 signaling domain-containing CAR T cells readily released sCD137 upon antigen recognition in a manner favored by the CD137 signaling domain. Patients treated intratumorally with low dose Urelumab showed increased plasma concentrations of sCD137. Conclusion: sCD137 in plasma and CD137 surface expression can be used as quantitative parameters dynamically reflecting therapeutic co-stimulatory activity elicited by agonist CD137-targeted agents. Citation Format: Javier Glez-Vaz, Arantza Azpilikueta, Irene Olivera, Assunta Cirella, Álvaro Teijeira, Carmen Ochoa, Maite Álvarez, Iñaki Eguren, Carlos Luri-Rey, Miguel F. Sanmamed, Ignacio Melero. Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 628.